tcrY Resolved · high auto-curated
H37Rv Rv3764c · MTBC0 - ·
475 aa · 4209582–4211009 (-) ·
RefSeq NP_218281.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | two component sensor kinase TcrY |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Two component sensor kinase TcrY. Pfam: HAMP (PF00672.31), HisKA (PF00512.32), HATPase_c (PF02518.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O69729
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable sensor histidine kinase TcrY |
| EC (curated) |
EC 2.7.13.3
|
| Curated function | Member of the two-component regulatory system TcrY/TcrX. Activates TcrX by phosphorylation. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | tcrY |
| eggNOG description | Histidine kinase |
| Orthologous group | COG0642 |
| EC number |
EC 2.7.13.3
|
| KEGG orthology |
K02484, K07656
|
| KEGG pathways |
map02020
|
| KEGG modules |
M00463
|
| Gene Ontology (49) |
GO:0000287, GO:0003674, GO:0003824, GO:0005488, GO:0005509, GO:0005515, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +37 more
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.565 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 15 missense, 0 nonsense, 0 frameshift |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
HAMP | PF00672.31 | 4.8e-06 | 174–233 | HAMP domain |
HisKA | PF00512.32 | 3.6e-19 | 248–312 | His Kinase A (phospho-acceptor) domain |
HATPase_c | PF02518.32 | 3.3e-27 | 355–465 | Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: tcrX (two component transcriptional regulator TcrX), high confidence from genomic context alone (score 985 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3765c tcrX |
two component transcriptional regulator TcrX | 993 | 985 ctx | neighborhood:793 cooccurence:772 coexpression:569 textmining:548 |
Rv1033c trcR |
two component transcriptional regulator TrcR | 915 | 899 ctx | cooccurence:766 |
Rv0491 regX3 |
two component sensory transduction protein RegX | 883 | 877 ctx | cooccurence:715 |
Rv0903c prrA |
two component transcriptional regulator PrrA | 901 | 874 ctx | cooccurence:710 |
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 881 | 871 ctx | cooccurence:702 |
Rv3246c mtrA |
two component DNA-binding response regulator MtrA | 885 | 870 ctx | cooccurence:703 |
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 888 | 858 ctx | cooccurence:672 |
Rv0981 mprA |
two-component response regulator MrpA | 859 | 851 ctx | cooccurence:654 |
Rv1027c kdpE |
transcriptional regulator KdpE | 852 | 824 ctx | cooccurence:592 |
Rv2884 |
transcriptional regulator | 798 | 786 ctx | cooccurence:504 |
Rv0818 |
transcriptional regulator | 756 | 741 ctx | cooccurence:407 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 760 | 731 | experimental:422 database:538 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 744 | 729 | database:590 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 725 | 714 | experimental:401 database:538 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase | 723 | 712 | experimental:401 database:538 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): two component sensor kinase TcrY
- Pfam (hmmscan --cut_ga): HAMP PF00672.31 (E=5e-06), HisKA PF00512.32 (E=4e-19), HATPase_c PF02518.32 (E=3e-27)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_218281.1)
- Domains: Pfam-A via hmmscan --cut_ga — HAMP (PF00672.31), HisKA (PF00512.32), HATPase_c (PF02518.32)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0642 - Curated reference: UniProt O69729 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
61 functional partner(s); context anchor
tcrX - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3764c|tcrY MGITAATEMALRRHLVAQLDNQLGGTSYRSVLMYPEKMPRPPWRHETHNYIRSGPGPRFLDAPGQPAGMVAAVVSDGTTVAAGYLTGSGSRAALTSTGRSQLERIAGSRTPLTLDLDGLGRYRVLAAPSRNGHDVIVTGLSMGNVDATMLQMLIIFGIVTVIALVAATTAGIVIIKRALAPLRRVAQTASEVVDLPLDRGEVKLPVRVPEPDANPSTEVGQLGSALNRMLDHIAAALSARQASETCVRQFVADASHELRTPLAAIRGYTELTQRIGDDPEAVAHAMSRVASETERITRLVEDLLLLARLDSGRPLERGPVDMSRLAVDAVSDAHVAGPDHQWALDLPPEPVVIPGDAARLHQVVTNLLANARVHTGPGTIVTTRLSTGPTHVVLQVIDNGPGIPAALQSEVFERFARGDTSRSRQAGSTGLGLAIVSAVVKAHNGTITVSSSPGYTEFAVRLPLDGWQPLESSPR